Phagocytic defense in the lung

Phagocytic defense in the normal lung is shared principally by two kinds of cells - alveolar macrophages that reside on the air surface and roam the alveoli and PMNs that circulate in the intravascular space or are stored transiently in areas adjacent to the capillary-alveolar interface (marginated in capillaries) and can reach the alveolar space quickly. The nature of the stimulating microorganism or aerosol particle reaching the alveolar surface may determine which phagocytic cell ultimately responds to contain the intruder. Ingestion and containment (either intracellular killing or enzymatic degradation) are the goals, and an 'opsonin' may be necessary to enhance the efficiency of phagocytosis. In the lung this is very complex, reflecting the interdependence on immune and nonimmune opsonins. For immune mediated phagocytosis by alveolar macrophages, IgG antibody is preferable. Among the four subclasses of IgG, certain ones seem to bind preferentially to macrophages, whereas others are already adherent to the cells as cytophilic antibody. In the respiratory tract milieu of subjects with CF, the interaction of immune and nonimmune opsonins is much more complex because of proteolytic enzymes that can degrade antibodies creating various fragments. Now that we are in an era of very specific humoral replacement therapy with intravenous IgG that contains IgG subclasses and the potential for using monoclonal antibodies for very precisely directed replacement, special attention must be given to identifying the appropriate class and subclass of antibody that may be required. This may be relatively simple when forms of passive immune therapy are being considered. More difficult will be devising ways to actively immunize patients (or animals) and manipulate their antibody responses so that selective immunoglobulin subclasses are produced. To obtain such control over the humoral immune response will require much more basic work in animal models. More attention to the form of immunizing antigen, type of adjuvant and site of administration will be required. Finally, selective immunization of the mucosal surfaces of the airways will present different challenges than parenteral methods that elicit systemic responses and may not be satisfactory to prevent certain respiratory infections. The prospects are exciting despite much work in cellular immunology that remains for the future.